Sensory neuropathy

The earliest reports of neurological complications of AIDS described distal symmetrical, painful sensory neuropathy occurring in HIV patients (Snider et al. 1983). Dysimmune inflammatory polyneuropathy was subsequently recognized as a complication of AIDS (Lipkin et al. 1985). Progressive polyneuropathy associated with cytomegalovirus (CMV) infection was documented as the first truly opportunistic infection of the peripheral nerve (Eidelberg et al. 1986). 

Distal sensory neuropathy AIDS Subacute or chronic Distal sensory loss and neuropathic pain depressed or absent ankle reflexes Immune dysfunction macrophage-mediated axonal injury... 

Diffuse infiltrative lymphocytosis syndrome AIDS Subacute Sjogren s-hke symmetric or asymmetric sensorimotor, painful, multiple mononeuritis or distal sensory neuropathy Angiocentric CDS hyperlymphocytosis in peripheral nerves vascular mural necrosis... 

The reported risk factors for HIV-associated sensory neuropathy are varied and may have changed since the availability of HAART. In the pre-HAART era, age, nutritional deficiencies, alcohol exposure, higher HIV viral load, and low CD4 counts (Moyle and Sadler 1998 Childs et al. 1999), as well as mood, other neurologic disorders and functional abnormalities (Schifitto et al. 2002) were neuropathy risk factors. In the HAART era, the use of NRTI (Cherry et al. 2006 Pettersen et al. 2006) and exposure to protease inhibitor (PI) medication (Pettersen et al. 2006 Smyth et al. 2007) are considered additional risk factors. Although hepatitis C mono-infection has been associated with peripheral nerve disease, and there is... 

A generalized systemic illness may accompany HIV seroconversion (Cooper et al. 1985). Guillain-Barre syndrome (GBS) (Piette et al. 1986), unilateral (Wiselka et al. 1987) or bilateral facial palsies (Wechsler and Ho 1989), bibra-chial palsy (Calabrese et al. 1987) and sensory neuropathy (Denning 1988) have been reported to occur during this process, usually within 1-2 weeks of the acute febrile illness. Spinal fluid analysis may show a mild to moderate mononuclear pleocytosis and a mild increase in protein levels. The precise relationship to HIV viral load in the cerebrospinal fluid (CSF) or plasma is unknown (Brew 2003). There is no proven therapy, but most patients recover spontaneously without any treatment. 

DIES-associated neuropathy has a variety of chnical presentations, including painful symmetric or asymmetric sensorimotor neuropathy, distal sensory neuropathy, mononeuritis multiplex, and demyelinating polyneuropathy (Gherardi et al. 1998). Cranial neuropathy without evidence of a more generahzed neuropathy may occur, typically as a facial nerve palsy in association with parotidomegaly (Itescu et al. 1990 Brew 2003). The neuropathy develops subacutely over days to weeks. In some cases, muscle weakness may be a result of an inflammatory myositis (Kazi et al. 1996). 

Few studies have focused on the pathological changes in the spinal cord associated with HIV neuropathy. Selective degeneration of the gracile tract in patients with sensory neuropathy, characterized by loss of axons and myelin sheaths in the... 

Fig. 4.3 Epidermal nerve fiber illustrated in a 50-pm vertical skin section, immunostained with the panaxonal marker anti-protein gene product 9.5. Skin section showing epidermal nerve fiber density arrows) in the distal leg of a healthy adult (a) and reduced epidermal nerve fiber density and degenerating fibers arrows) in the distal leg of a HIV-associated sensory neuropathy patient (b) (scale bar, 50 pm). Courtesy of Drs Gigi Ebenezer and Justin McArthur, Johns Hopkins University, Baltimore, Maryland, USA...

Early attempts to find an animal model of HIV-associated sensory neuropathy met with little success. One group described a rabbit model of ddC-induced sensory neuropathy (Anderson et al. 1992). 

Currently, treatment of DSP and ATN is similar to many other neuropathies that have predominantly painful sensory involvement (Mendell and Sahenk 2003 Gonzalez-Duarte et al. 2007). It is purely symptomatic as there are no proven regenerative therapies to reverse the underlying process. An 8-month prospective pilot study reported an improvement in subjective quantitative sensory testing (QST) in HIV-infected patients who responded to HAART (Martin et al. 2000). The patients who did not respond to HAART did not show any improvements in QST. It is possible that suppression of viral load will slow the progression of DSP. Some studies have found a correlation between viral load and incidence (Childs et al. 1999), or severity (Simpson et al. 2002) of sensory neuropathy. Others, however, did not find any correlation between plasma viral loads and incidence of DSP or ATN (Brew et al. 2003). 

Abrams DI, Jay CA et al (2007) Cannabis in painful HIV-associated sensory neuropathy a randomized placebo-controUed trial. Neurology 68(7) 515-521 Anderson TD, Davidovich A et al (1992) Peripheral neuropathy induced by 2 , 3 -dideoxycytidine. 

Cornblath DR, Hoke A (2006) Recent advances in HIV neuropathy. Curr Opin Neurol 19(5) 446-450 Cornblath DR, McArthur JC (1988) Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex. Neurology 38(5) 794-796 Cornblath DR, McArthur JC et al (1987) Inflammatory demyeUnating peripheral neuropathies associated with human T-cell lymphotropic virus type III infection. Ann Neurol 21(l) 32-40 Corral I, Quereda C et al (1997) Acute poly radiculopathies in HIV-infected patients. J Neurol 244(8) 499-504... 

Holland NR, Stocks A et al (1997) Intraepidermal nerve fiber density in patients with painful sensory neuropathy. Neurology 48(3) 708-711... 

Kennedy JM, Hoke A et al (2004) Peripheral neuropathy in lentivirus infection evidence of inflammation and axonal injury. AIDS 18(9) 1241-1250 Keswani SC, Pardo CA et al (2002) HIV-associated sensory neuropathies. AIDS 16(16) 2105-2117... 

Keswani SC, Jack C et al (2006) Establishment of a rodent model of HIV-associated sensory neuropathy. J Neurosci 26(40) 10299-10304... 

Martin C, Solders G et al (2000) Antiretroviral therapy may improve sensory function in HIV-infected patients a pilot study. Neurology 54(11) 2120-2127 Masjuan J, Corral I et al (1997) Mycobacterial acute lumbosacral polyradiculopathy as the initial manifestation of AIDS. J Acquir Immune Defic Syndr Hum Retrovirol 15(2) 175 McArthur JC, Yiannoutsos C et al (2000) A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. AIDS Clinical Trials Group Team 291. Neurology 54(5) 1080-1088... 

McCarthy BG, Hsieh ST et al (1995) Cutaneous innervation in sensory neuropathies evaluation by skin biopsy. Neurology 45(10) 1848-1855... 

MeUi G, Keswani SC et al (2006) Spatially distinct and functionally independent mechanisms of axonal degeneration in a model of HIV-associated sensory neuropathy. Brain 129(Pt 5) 1330-1338 MendeU JR, Sahenk Z (2003) Clinical practice. Painful sensory neuropathy. N Engl J Med 348(13) 1243-1255... 

Pettersen JA, Jones G et al (2006) Sensory neuropathy in human immunodeficiency virus/acquired immunodeficiency syndrome patients protease inhibitor-mediated neurotoxicity. Ann Neurol... 

Polydefkis M, Yiannoutsos CT et al (2002) Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy. Neurology 58(1) 115-119 Power C, Gill MJ et al (2002) Progress in clinical neurosciences The neuropathogenesis of HIV infection host-virus interaction and the impact of therapy. Can J Neurol Sci 29(l) 19-32 Premack BA, SchaU TJ (1996) Chemokine receptors gateways to inflammation and infection. Nat Med 2(11) 1174-1178... 

Ranee NE, McArthur JC et al (1988) GracUe tract degeneration in patients with sensory neuropathy and AIDS. Neurology 38(2) 265-271... 

Zhu Y, Antony J et al (2006) CD8-t lymphocyte-mediated injury of dorsal root ganghon neurons during lentiviras infection CD 154-dependent ceU contact neurotoxicity. J Neurosci 26(13) 3396-3403 Zhu Y, Antony JM et al (2007) Didanosine causes sensory neuropathy in an HIV/AIDS animal model impaired mitochondrial and neurotrophic factor gene expression. Brain 130(Pt 8) 2011-2023... 

Paraneoplastic sensory neuropathy Lambert-Eaton myasthenic syndrome Neuromyotonia (Isaacs syndrome)... 

Gao, W. Q., Dybdal, N., Shinsky, N. et al. Neurotrophin-3 reverses experimental cisplatin-induced peripheral sensory neuropathy. Ann. Neurol. 38 30-37,1995. 

Helgren, M. E., Cliffer, K. D., Torrento, K. et al. Neurotrophin-3 administration attenuates deficits of pyridoxine-induced large-fiber sensory neuropathy. J. Neurosci. 17 372-382,1997. 

Shy, M. E., Garbern, J. Y. and Kamholz, J. Hereditary motor and sensory neuropathies a biological perspective. Lancet Neurol. 1 110-118,2002. 

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